Article Text

  1. C. J. Glueck,
  2. J. Pranikoff,
  3. D. Aregawi,
  4. M. Haque,
  5. S. Dharashivkar,
  6. T. Tracy,
  7. P. Wang
  1. Jewish Hospital, Cincinnati


We hypothesized that the thrombophilic G1691A Factor V Leiden gene mutation was a common, significant, treatable cause of sporadic miscarriage. We used PCR techniques to characterize thrombophilic (G1691A V Leiden [FV], G20210A prothrombin, C677T/A1298C MTHFR) and hypofibrinolytic (plasminogen activator inhibitor activity [PAI-1] 4G4G) gene mutations. We carried out serologic measures of thrombophilia (homocysteine, ACLA IgG and IgM, lupus anticoagulant, Factor VIII, Factor XI, protein C, total and free protein S, antithrombin III) and hypofibrinolysis (plasminogen activator inhibitor activity [PAI-Fx]), Lp[a]). We compared thrombophilia-hypofibrinolysis in 89 women (83 white, 4 black, 2 other) with ≥ 1 pregnancy and 1 miscarriage (139 live births, 89 miscarriages) and in 363 women (338 white, 21 black, 4 other) with ≥ 1 pregnancy and 0 miscarriages (901 live births). Of the 363 women in the 0 miscarriage group, 8 (2.2%) had FV heterozygosity vs 11 heterozygous and 2 homozygous FV women in the sporadic miscarriage group (14.6%), p<.0001. PAI-Fx was high (≥ 21.1 U/mL) in 19/59 women (32%) in the 1 miscarriage group vs 24/144 (17%) in the 0 miscarriage group (p = .014). PAI-Fx remained higher in cases (19/59, 32%) than controls (5/38, 13%), p = .03, after matching for BMI, and race (89 pairs). After matching cases vs controls by age, BMI, and race (74 pairs), high Factor VIII (> 150%) was more common in cases (11/33, 33%) than controls (3/28, 11%), p = .04.There were no other group differences (p>0.05) in measures of thrombophilia and hypofibrinolysis. After unexplained sporadic miscarriage, we suggest that measurements be done of the FV mutation, PAI-Fx, and Factor VIII. Recognition of FV heterozygosity-homozygosity or high Factor VIII after sporadic miscarriage allows prospective thromboprophylaxis with enoxaparin (60-80 mg/day) to optimize live birth outcomes in subsequent pregnancies. High PAI-Fx can often be lowered with Glucophage (2.5 g/day) to further optimize live birth outcomes.

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